The etiologies of many human neoplasms such as breast cancer, pituitary tumors, and cancer of the prostate, involve poorly understood interactions between hormones and glandular epithelium. Advancement in our knowledge of the mechanisms underlying hormonal influences on carcinogenesis could lead to better management of these diseases. Therefore, we intend to investigate a recently discovered animal model system of pituitary primordium (Rathke's Pouch, RP)-derived tumors that promises to serve as an important model for secretory neoplasm in general. Our experiments will analyze the role of hormones on tumorigenesis and the relationship of their influences to various stages of differentiation in the induced tissue (Rathke's Pouch). Preliminary studies have demonstrated that the rat pituitary primordium, microsurgically isolated at certain precise stages in ontogeny and transplanted into the median eminence of adults, invariably gives rise to large tumors. These neoplasms often closely resemble human pituitary tumors and teratocarcinomas. They secrete adenohypophyseal hormones and consist of areas of chromophobe adenomas and other areas of mixed cell types. Extra-cranial grafts (kidney capsule or testis) of pituitary primordia form small benign nodules and not large tumors, suggesting that certain brain/median eminence factors critically influence tumor development. In this research proposal we delineate our plans to further characterize this unique model system. On both the ultrastructural and molecular level, tumor-susceptible (12-day RP) and non-susceptible (15-day RP) embryonic tissue will be compared jointly and with normal mature and transformed adenohypophyseal cells. Tumor development and secretory activity will be examined in homotopic and heterotopic sites and by in vitro studies to determine the effects of neurohormones on tumorigenesis. Morphological characterization of the tumor cells will be by light and electron microscopy. The actual secretion of several hormones will be monitored by radioimmunoassay (RIA).